The adhesion of transformed cells is defective when compared with their normal counterparts, a property which potentially plays an important role in metastasis. The basis for this defect will be sought in terms of changes in the cell-to-substrate contracts developed by transformed cells. The contracts will be evaluated by interference reflection microscopy. The study will center on the focal contact, the stronger substrate adhesion, but include the close contact. In order to further understand the basis of the defective adhesion, an ultrastructural (HVEM) and immunochemical study will be undertaken in normal cells of the development the cytoplasmic precursor of the focal contact and changes in the precursor after the contact is made. In addition, experiments exploiting a non-transformed adhesion-defective mutant are planned to evaluate the relative roles of different cell surface glycoconjugates in forming the substrate contracts in normal cells. A method is given to isolate specific cell surface proteins involved in substrate adhesion. Defects in the various steps in forming the cytoplasmic precursor, and in the required cell surface glycoconjugates, will be sought in order to explain changes in the substrate contracts and hence adhesion of transformed cells. The significance of low levels of fibronectin on transformed cells will be evaluated in terms of its role in the formation of the two substrate contacts. Spontaneously, chemically and virally transformed cells will be examined.